Decreased striatal dopaminergic responsiveness in detoxified cocaine- dependent subjects

N. D. Volkow, G. J. Wang, J. S. Fowler, J. Logan, S. J. Gatley, Robert Hitzemann, A. D. Chen, S. L. Dewey, N. Pappas

Research output: Contribution to journalArticle

654 Citations (Scopus)

Abstract

Cocaine blocks the reuptake of dopamine, a neurotransmitter involved in the control of movement, cognition, motivation and reward. This leads to an increase in extracellular dopamine; the reinforcing effect of cocaine is associated with elevated dopamine levels in the nucleus accumbens. But addiction to cocaine involves other effects, such as craving, loss of control and compulsive drug intake; the role of the dopamine system in these effects is less well-understood. We therefore used positron emission tomography (PET) to compare the responses of cocaine addicts and normal controls to intravenous methylphenidate, a drug that, like cocaine, causes an increase in synaptic dopamine. Addicts showed reduced dopamine release in the striatum, the brain region where the nucleus accumbens is located, and also had a reduced 'high' relative to controls. In contrast, addicts showed an increased response to methylphenidate in the thalamus (a region that conveys sensory input to the cortex). This thalamic response was associated with cocaine craving and was not seen in control subjects. Thus, our findings challenge the notion that addiction involves an enhanced striatal dopamine response to cocaine and/or an enhanced induction of euphoria. Moreover, they suggest a participation of thalamic dopamine pathways in cocaine addiction, a possibility that merits further investigation.

Original languageEnglish (US)
Pages (from-to)830-833
Number of pages4
JournalNature
Volume386
Issue number6627
StatePublished - Apr 24 1997
Externally publishedYes

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Corpus Striatum
Cocaine
Dopamine
Cocaine-Related Disorders
Methylphenidate
Nucleus Accumbens
Drug and Narcotic Control
Thalamus
Reward
Positron-Emission Tomography
Cognition
Neurotransmitter Agents
Motivation
Brain

ASJC Scopus subject areas

  • General

Cite this

Volkow, N. D., Wang, G. J., Fowler, J. S., Logan, J., Gatley, S. J., Hitzemann, R., ... Pappas, N. (1997). Decreased striatal dopaminergic responsiveness in detoxified cocaine- dependent subjects. Nature, 386(6627), 830-833.

Decreased striatal dopaminergic responsiveness in detoxified cocaine- dependent subjects. / Volkow, N. D.; Wang, G. J.; Fowler, J. S.; Logan, J.; Gatley, S. J.; Hitzemann, Robert; Chen, A. D.; Dewey, S. L.; Pappas, N.

In: Nature, Vol. 386, No. 6627, 24.04.1997, p. 830-833.

Research output: Contribution to journalArticle

Volkow, ND, Wang, GJ, Fowler, JS, Logan, J, Gatley, SJ, Hitzemann, R, Chen, AD, Dewey, SL & Pappas, N 1997, 'Decreased striatal dopaminergic responsiveness in detoxified cocaine- dependent subjects', Nature, vol. 386, no. 6627, pp. 830-833.
Volkow ND, Wang GJ, Fowler JS, Logan J, Gatley SJ, Hitzemann R et al. Decreased striatal dopaminergic responsiveness in detoxified cocaine- dependent subjects. Nature. 1997 Apr 24;386(6627):830-833.
Volkow, N. D. ; Wang, G. J. ; Fowler, J. S. ; Logan, J. ; Gatley, S. J. ; Hitzemann, Robert ; Chen, A. D. ; Dewey, S. L. ; Pappas, N. / Decreased striatal dopaminergic responsiveness in detoxified cocaine- dependent subjects. In: Nature. 1997 ; Vol. 386, No. 6627. pp. 830-833.
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